Objective To explore the clinical efficacy and safety of duloxetine in combination with small-dosage paliperidone in the treatment of somatization disorder. Methods A total of 63 patients with somatization disorder were randomly divided into a study group (32 cases) and a control group (31 cases), treated with duloxetine in combination with paliperidone and duloxetine alone, respectively, for 8 weeks. The clinical efficacy and side effects were evaluated at the end of 2, 4, 6 and 8 weeks, and compared with beforetreatment, using Screening for Somatoform Symptoms-7 (SOMS-7), Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Scale (HAMA) and Treatment Emergent Symptom Scale (TESS). Results For both the study group and control group, scores on SOMS-7, HAMD and HAMA were significantly lower after treatment than before treatment (P<0.01). At the end of the 8th week, the effective rates of the study group and the control group were 87.5% and 64.6%, respectively, and the effectual rates of the two group were 62.5% and 29.1%, respectively , for both categories, with the differences being significant (P<0.05 or P<0.01). At the end of the second week, the HAMD score for the study group was significantly lower than for the control group (P<0.01). There were no significant differences between the two groups in ADR rates (P>0.05). Conclusions For the treatment of somatization disorder, duloxetine in combination with small-dosage paliperidone worked better and faster than duloxetine alone, without added side effects.